Viability and Outcomes With Revascularization or Medical Therapy in Ischemic Ventricular Dysfunction

Key Points Question Does myocardial viability testing identify patients with ischemic left ventricular dysfunction who benefit from percutaneous coronary intervention? Findings In this prespecified subgroup analysis of a randomized clinical trial of 610 participants with ischemic left ventricular dysfunction 35% or less, myocardial viability testing with cardiovascular magnetic resonance imaging or stress echocardiography did not identify a population of patients who benefit from percutaneous coronary intervention. The extent of nonviable myocardium was associated with a higher risk of death or hospitalization for heart failure and a lower chance of improvement in left ventricular function. Meaning Findings suggest that the extent of dysfunctional yet viable myocardium was not associated with revascularization outcomes.

This supplementary material has been provided by the authors to give readers additional information about their work.

eAppendix 1. Revived Sites and Investigators
This list is ordered by the number of patients enrolled by each center.There were many more individuals who made contributions to the REVIVED-BCIS2 Trial at each participating center, but have not been named below; we are very grateful for their efforts.OMT -optimal medical therapy.PCI -percutaneous coronary intervention.Data are presented as cubic splines -these were not specified in the statistical analysis plan but are presented for clarity of visualisation of the data.Dotted lines represent 95% confidence intervals.
Figure e1B -The extent of non-viable myocardium (continuous) OMT -optimal medical therapy.PCI -percutaneous coronary intervention.Data are presented as cubic splines -these were not specified in the statistical analysis plan but are presented for clarity of visualisation of the data.Dotted lines represent 95% confidence intervals.
Figure e1C -Scar burden (continuous) OMT -optimal medical therapy.PCI -percutaneous coronary intervention.Data are presented as cubic splines -these were not specified in the statistical analysis plan but are presented for clarity of visualisation of the data.Dotted lines represent 95% confidence intervals.
eFigure 2. Interaction between treatment assignment, viability characteristics (in tertiles) and primary outcome The data above only include patients for whom paired baseline and 6-month echocardiograms were available (without imputation).The imputed datasets (n=578 and n=554 at 6-and 12-months respectively) have been used when calculating the odds ratios of the primary outcome by LV improvement in the main manuscript.Patients who experienced a primary outcome event in the first six months were excluded from the imputed and nonimputed analyses.See also table S7.

eAppendix 1 . 2 . 1 . 4 . 5 . 1 . 2 . 3 . 5 . 6 . 7 .
Revived Sites and Investigators eAppendix Trial Organization and Oversight eFigure Relationship Between Viability Characteristics and the Primary Outcome by Treatment Assignment eFigure 2. Interaction Between Treatment Assignment, Viability Characteristics (in Tertiles) and Primary Outcome eFigure 3. Interaction Between Treatment Assignment, Viability Characteristics (in Tertiles) and Likelihood of Left Ventricular Improvement at 6-Months eFigure Improvement in Left Ventricular Ejection Fraction at 12 Months eFigure Impact of Improvement in Left Ventricular Function at 6 Months on Subsequent Occurrence of Primary Outcome (Landmark Analysis) eTable Baseline Demographics in Patients Who Had CMR, DSE or Were Excluded eTable Primary and Clinical Secondary Outcomes eTable Interaction Between Treatment Assignment, Viability Characteristics (Continuous) and Outcomes eTable 4. Relationship Between Viability Characteristics (Continuous) and Outcomes eTable Sensitivity Analysis (Incorporating 50% LGE Transmurality Threshold) of Interaction Between Treatment Assignment, Viability Characteristics (Continuous) and Primary Outcome eTable Change in Left Ventricular Ejection Fraction From Baseline to 6-and 12-Month Follow-Up eTable Determinants of Binary Improvement in Left Ventricular Ejection Fraction at 6-and 12-Months eReferences.

Dobutamine Stress Echocardiography Core Laboratory
Prof Andrew Clark, Chair of Clinical Cardiology, Castle Hill Hospital, Hull (Chair) Mrs Helen Williams, Pharmacist, NHS Southwark Clinical Commissioning Group, London Dr Pablo Perel, Epidemiologist, London School of Hygiene & Tropical Medicine Dr David Walker, Consultant Cardiologist, Conquest Hospital, St. Leonards-on-Sea Ms Marilou Huang (Reader), King's College Hospital, London Ms Sandya Nandakumar (Reader), King's College Hospital, London Dr Joseph Okafor (Reader), Guy's and St Thomas' NHS Foundation Trust, London Dr Oleksandr Danylenko (Reader), Guy's and St Thomas' NHS Foundation Trust, London Committees and Oversight Prof Rod Stables, Consultant Cardiologist, Liverpool Heart and Chest Hospital Prof Divaka Perera, Chief Investigator, King's College London Ms Liz Bestic, Patient, Carer and Public representative Mrs Paula Young, Patient, Carer and Public representative Mrs Helen Datta, Patient, Carer and Public representative Mr Jeremy Dearling, Patient, Carer and Public representative Data and Safety Monitoring Committee Prof Peter Ludman, Consultant Cardiologist, Queen Elizabeth Hospital, Birmingham (Chair) Dr Suzanna Hardman, Consultant Cardiologist, The Whittington Hospital, London Prof Louise Brown, Senior Statistician, MRC Clinical Trials Unit at University College London Clinical Events Committee Prof Roxy Senior, Professor of Cardiology, Royal Brompton Hospital, London (Chair) Dr Zaheer Yousef, Consultant Cardiologist, University Hospital of Wales Dr Rajan Sharma, Consultant Cardiologist, St George's Hospital, London Prof Tim Clayton, London School of Hygiene & Tropical Medicine Mr Richard Evans, London School of Hygiene & Tropical Medicine Ms Ruth Canter, London School of Hygiene & Tropical Medicine Mr Steven Robertson, London School of Hygiene & Tropical Medicine Mrs Sophie Arnold, Guy's and St Thomas' Hospital, London Dr Bhavik Modi, King's College London Dr Matthew Ryan, King's College London Dr Holly Morgan, King's College London Mrs Rosemary Knight, London School of Hygiene & Tropical Medicine Miss Rebecca Matthews, London School of Hygiene & Tropical Medicine Mrs Lucy Clack, Guy's and St Thomas' Hospital, London Ms Josenir Astarci, London School of Hygiene & Tropical Medicine (Admin)

eTable 1. Baseline demographics in patients who had CMR, DSE or were excluded*
Plus-minus values are means ±SD.Percentages may not total 100 because of rounding.19 patients underwent assessment with single photon emission computed tomography and 11 with positron emission tomography.BCIS denotes British Cardiovascular Intervention Society, CMR cardiovascular magnetic resonance imaging, CRT cardiac resynchronization therapy, DSE dobutamine stress echocardiography, ICD implantable cardioverter defibrillator, IQR interquartile range, RAAS renin angiotensin aldosterone system.† The British Cardiovascular Intervention Society (BCIS) jeopardy score is a quantification of the extent of myocardial jeopardy relating to clinically significant coronary artery stenoses.The score ranges from 0 (no significant coronary disease) to 12 (disease jeopardizing the whole left ventricular myocardium).‡Baseline left ventricular ejection fraction measured by the blinded echocardiography core laboratory.

Change in left ventricular ejection fraction from baseline to 6-and 12- month follow-up
(-2.9 to 14.6) 5.0 (-3.6 to 14.1) 5.2 (-3.2 to 14.2) IQR -interquartile range.OMT -optimal medical therapy.PCI -percutaneous coronary intervention.SE -standard error.Data above include imputation for missing values, as described in the main manuscript Table e7C -Interaction between treatment assignment, viability characteristics (continuous) and likelihood of left ventricular improvement at 12-months CI -confidence interval.LV -left ventricle.OMT -optimal medical therapy.PCIpercutaneous coronary intervention